Universität zu Köln

Kolovos, Petros ORCID: 0000-0002-0787-6158, Georgomanolis, Theodore, Koeferle, Anna, Larkin, Joshua D., Brant, Lilija, Nikolic, Milos ORCID: 0000-0003-0029-7601, Gusmao, Eduardo G., Zirkel, Anne, Knoch, Tobias A., van Ijcken, Wilfred F., Cook, Peter R., Costa, Ivan G. ORCID: 0000-0003-2890-8697, Grosveld, Frank G. and Papantonis, Argyris ORCID: 0000-0001-7551-1073 (2016). Binding of nuclear factor kappa B to noncanonical consensus sites reveals its multimodal role during the early inflammatory response. Genome Res., 26 (11). S. 1478 - 1490. COLD SPRING HARBOR: COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT. ISSN 1549-5469

Full text not available from this repository.

Abstract

Mammalian cells have developed intricate mechanisms to interpret, integrate, and respond to extracellular stimuli. For example, tumor necrosis factor (TNF) rapidly activates proinflammatory genes, but our understanding of how this occurs against the ongoing transcriptional program of the cell is far from complete. Here, we monitor the early phase of this cascade at high spatiotemporal resolution in TNF-stimulated human endothelial cells. NF-kappa B, the transcription factor complex driving the response, interferes with the regulatory machinery by binding active enhancers already in interaction with gene promoters. Notably, >50% of these enhancers do not encode canonical NF-kappa B binding motifs. Using a combination of genomics tools, we find that binding site selection plays a key role in NF-kappa B-mediated transcriptional activation and repression. We demonstrate the latter by describing the synergy between NF-kappa B and the corepressor JDP2. Finally, detailed analysis of a 2.8-Mbp locus using sub-kbp-resolution targeted chromatin conformation capture and genome editing uncovers how NF-kappa B that has just entered the nucleus exploits pre-existing chromatin looping to exert its multimodal role. This work highlights the involvement of topology in cis-regulatory element function during acute transcriptional responses, where primary DNA sequence and its higher-order structure constitute a regulatory context leading to either gene activation or repression.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kolovos, Petros UNSPECIFIED orcid.org/0000-0002-0787-6158 UNSPECIFIED Georgomanolis, Theodore UNSPECIFIED UNSPECIFIED UNSPECIFIED Koeferle, Anna UNSPECIFIED UNSPECIFIED UNSPECIFIED Larkin, Joshua D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Brant, Lilija UNSPECIFIED UNSPECIFIED UNSPECIFIED Nikolic, Milos UNSPECIFIED orcid.org/0000-0003-0029-7601 UNSPECIFIED Gusmao, Eduardo G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Zirkel, Anne UNSPECIFIED UNSPECIFIED UNSPECIFIED Knoch, Tobias A. UNSPECIFIED UNSPECIFIED UNSPECIFIED van Ijcken, Wilfred F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Cook, Peter R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Costa, Ivan G. UNSPECIFIED orcid.org/0000-0003-2890-8697 UNSPECIFIED Grosveld, Frank G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Papantonis, Argyris UNSPECIFIED orcid.org/0000-0001-7551-1073 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-257287
DOI:	10.1101/gr.210005.116
Journal or Publication Title:	Genome Res.
Volume:	26
Number:	11
Page Range:	S. 1478 - 1490
Date:	2016
Publisher:	COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
Place of Publication:	COLD SPRING HARBOR
ISSN:	1549-5469
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CHROMOSOME CONFORMATION CAPTURE; GENERATION SEQUENCING DATA; RNA-SEQ DATA; GLUCOCORTICOID-RECEPTOR; SUPER-ENHANCER; TRANSCRIPTION FACTORIES; GENOMIC INTERACTIONS; CELL IDENTITY; GENES; CHROMATIN Multiple languages Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/25728